Drug-Induced Liver Injury
Drug- and toxin-induced liver injury is responsible for a significant amount of morbidity and mortality. A very wide range of clinical and pathologic presentations may result. The time of onset after drug exposure varies from hours to months. The clinical
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Drug-Induced Liver Injury
Drug- and toxin-induced liver injury is responsible for a significant amount of morbidity and mortality. A very wide range of clinical and pathologic presentations may result. The time of onset after drug exposure varies from hours to months. The clinical manifestations range from asymptomatic deranged liver function to fulminant hepatic failure and death. Drug- or toxin-induced liver injuries can mimic all forms of acute, chronic, vascular, or neoplastic liver diseases that are caused by other aetiologies; hence, they always are included in the differential diagnosis of virtually any form of liver disease. Drug/toxin reactions may be intrinsic or predictable, in cases in which they are dose dependent (e.g., paracetamol, carbon tetrachloride), or idiosyncratic and unpredictable, when they are dose independent (e.g., isoniazid, halothane). The underlying mechanisms include direct/indirect toxicity, aberrant metabolism producing toxic metabolites, and immune-mediated hypersensitivity. The diagnosis of drug- or toxin-induced liver injuries requires clinical, biochemical, and pathologic correlation. Recognition of the overall morphologic pattern in the pathologic examination is essential in the diagnostic process. The morphologic patterns may be categorized as those associated with (1) necroinflammatory injury, (2) cholestatic injury, (3) steatosis and steatohepatitis, (4) vascular lesions, (5) neoplasm and neoplasm-like lesions, and (6) adaptive change.
8.1
Necroinflammatory Injury
Fig. 8.1 Acute hepatic necrosis induced by paracetamol. Extensive zone 3 necrosis is accompanied by a mild inflammatory infiltrate. Drug/ toxin-induced acute hepatic necrosis typically has an abrupt onset, with latency within 2 weeks. Patients usually present with malaise, nausea, and abdominal pain. Hepatic encephalopathy may occur early. Dysfunction or failure of other organs (kidney, lung, and bone marrow) and sepsis related to immunoparesis may complicate the clinical picture. Markedly elevated (>20× upper normal limit) serum aminotransferase levels with normal or modestly elevated (
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